ZNF48 is a zinc finger protein that functions as a transcriptional regulator. The protein contains zinc finger domains enabling DNA binding and transcriptional regulation through RNA polymerase II 1, with capacity for protein-protein interactions in the nucleus 1. ZNF48 serves as a component of a six-gene signature (NAT10, DDX27, ZNF48, C8ORF33, MOCS3, MPP6) marking oncogene-induced replication stress (ORS) in aggressive cancers 1. This signature identifies tumors with elevated replication stress, particularly in diffuse large B cell lymphoma, ovarian cancer, triple-negative breast cancer, and colorectal carcinoma 1. The ORS signature has been applied to osteosarcoma stratification, where ZNF48 expression levels differentiate patient cohorts with distinct survival outcomes 2. Beyond cancer, ZNF48 was identified as a candidate gene in whole-exome sequencing studies of cryptorchidism in pigs, suggesting involvement in developmental pathways 3. In neuropsychiatric conditions, ZNF48 expression distribution correlates with brain functional signatures specific to post-traumatic stress disorder complicated by cognitive impairment, implicating cortisol-induced neurotoxicity mechanisms 4. Clinically, ZNF48 represents a potential biomarker for identifying high-risk cancer patients and stratifying treatment approaches targeting replication stress pathways.